scholarly journals Sialic Acid Transport Contributes to Pneumococcal Colonization

2010 ◽  
Vol 79 (3) ◽  
pp. 1262-1269 ◽  
Author(s):  
Carolyn Marion ◽  
Amanda M. Burnaugh ◽  
Shireen A. Woodiga ◽  
Samantha J. King
Keyword(s):  
Sialic Acid ◽  
Carbon Source ◽  
Sole Carbon Source ◽  
Upper Respiratory Tract ◽  
Acid Transport ◽  
Upper Respiratory ◽  
Pneumococcal Colonization ◽  
Free Carbohydrates ◽  
Airway Colonization

ABSTRACTStreptococcus pneumoniaeis a major cause of pneumonia and meningitis. Airway colonization is a necessary precursor to disease, but little is known about how the bacteria establish and maintain colonization. Carbohydrates are required as a carbon source for pneumococcal growth and, therefore, for colonization. Free carbohydrates are not readily available in the naso-oropharynx; however, N- and O-linked glycans are common in the airway. Sialic acid is the most common terminal modification on N- and O-linked glycans and is likely encountered frequently byS. pneumoniaein the airway. Here we demonstrate that sialic acid supports pneumococcal growth when provided as a sole carbon source. Growth on sialic acid requires import into the bacterium. Three genetic regions have been proposed to encode pneumococcal sialic acid transporters: one sodium solute symporter and two ATP binding cassette (ABC) transporters. Data demonstrate that one of these,satABC, is required for transport of sialic acid. AsatABCmutant displayed significantly reduced growth on both sialic acid and the human glycoprotein alpha-1. The importance ofsatABCfor growth on human glycoprotein suggests that sialic acid transport may be importantin vivo. Indeed, thesatABCmutant was significantly reduced in colonization of the murine upper respiratory tract. This work demonstrates thatS. pneumoniaeis able to use sialic acid as a sole carbon source and that utilization of sialic acid is likely important during pneumococcal colonization.

scholarly journals Neuraminidase B controls neuraminidase A-dependent mucus production and evasion

2020 ◽  
Author(s):  
Alexandria J. Hammond ◽  
Ulrike Binsker ◽  
Surya D. Aggarwal ◽  
Mila Brum Ortigoza ◽  
Cynthia Loomis ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Sialic Acid ◽  
Mucociliary Clearance ◽  
Dependent Manner ◽  
Upper Respiratory Tract ◽  
Mucus Production ◽  
Upper Respiratory ◽  
Stimulation Of

AbstractBinding of Streptococcus pneumoniae (Spn) to nasal mucus leads to entrapment and clearance via mucociliary activity during colonization. To identify Spn factors allowing for evasion of mucus binding, we used a solid-phase adherence assay with immobilized mucus of human and murine origin. Spn bound large mucus particles through interactions with carbohydrate moieties. Mutants lacking neuraminidase (nanA) or neuraminidase B (nanB) showed increased mucus binding that correlated with diminished removal of terminal sialic acid residues on bound mucus. The non-additive activity of the two enzymes raised the question why Spn expresses two neuraminidases and suggested they function in the same pathway. Transcriptional analysis demonstrated expression of nanA depends on the enzymatic function of NanB. As transcription of nanA is increased in the presence of sialic acid, our findings suggest that sialic acid liberated from host glycoconjugates by the secreted enzyme NanB induces the expression of the cell-associated enzyme NanA. The absence of detectable mucus desialylation in the nanA mutant, in which NanB is still expressed, suggests that NanA is responsible for the bulk of the modification of host glycoconjugates. Thus, our studies describe a functional role for NanB in sialic acid sensing in the host. The contribution of the neuraminidases in vivo was then assessed in a murine model of colonization. Although mucus-binding mutants showed an early advantage, this was only observed in a competitive infection, suggesting a complex role of neuraminidases. Histologic examination of the upper respiratory tract demonstrated that Spn stimulates mucus production in a neuraminidase-dependent manner. Thus, an increase production of mucus containing secretions appears to be balanced, in vivo, by decreased mucus binding. We postulate that through the combined activity of its neuraminidases, Spn evades mucus binding and mucociliary clearance, which is needed to counter neuraminidase-mediated stimulation of mucus secretions.Author SummaryStreptococcus pneumoniae (Spn) is a leading mucosal pathogen, whose host interaction begins with colonization of the upper respiratory tract. While there has been extensive investigation into bacterial interaction with epithelial cells, there is little understanding of bacterial-mucus interactions. Our study used mucus of human and murine origin and a murine model of colonization to study mucus associations involving Spn. The main findings reveal i) the enzymatic activity of Spn’s neuraminidases (NanA and NanB) contribute to mucus evasion through removing terminal sialic acid, ii) the enzymatic activity of NanB controls expression of the main neuraminidase, NanA, and iii) Spn induces sialic acid containing mucus secretions in vivo in a neuraminidase-dependent manner. We postulate that during colonization, neuraminidase-dependent reduction in mucus binding enables evasion of mucociliary clearance, which is necessary to counter neuraminidase-mediated stimulation of mucus secretions. Thus, our study provides new insights into the role of Spn neuraminidases on colonization.

scholarly journals Neuraminidase B controls neuraminidase A-dependent mucus production and evasion

2021 ◽  
Vol 17 (4) ◽  
pp. e1009158
Author(s):  
Alexandria J. Hammond ◽  
Ulrike Binsker ◽  
Surya D. Aggarwal ◽  
Mila Brum Ortigoza ◽  
Cynthia Loomis ◽  
...  
Keyword(s):  
Sialic Acid ◽  
Solid Phase ◽  
Transcriptional Analysis ◽  
Dependent Manner ◽  
Upper Respiratory Tract ◽  
Mucus Production ◽  
Enzymatic Function ◽  
Upper Respiratory

Binding of Streptococcus pneumoniae (Spn) to nasal mucus leads to entrapment and clearance via mucociliary activity during colonization. To identify Spn factors allowing for evasion of mucus binding, we used a solid-phase adherence assay with immobilized mucus of human and murine origin. Spn bound large mucus particles through interactions with carbohydrate moieties. Mutants lacking neuraminidase A (nanA) or neuraminidase B (nanB) showed increased mucus binding that correlated with diminished removal of terminal sialic acid residues on bound mucus. The non-additive activity of the two enzymes raised the question why Spn expresses two neuraminidases and suggested they function in the same pathway. Transcriptional analysis demonstrated expression of nanA depends on the enzymatic function of NanB. As transcription of nanA is increased in the presence of sialic acid, our findings suggest that sialic acid liberated from host glycoconjugates by the secreted enzyme NanB induces the expression of the cell-associated enzyme NanA. The absence of detectable mucus desialylation in the nanA mutant, in which NanB is still expressed, suggests that NanA is responsible for the bulk of the modification of host glycoconjugates. Thus, our studies describe a functional role for NanB in sialic acid sensing in the host. The contribution of the neuraminidases in vivo was then assessed in a murine model of colonization. Although mucus-binding mutants showed an early advantage, this was only observed in a competitive infection, suggesting a complex role of neuraminidases. Histologic examination of the upper respiratory tract demonstrated that Spn stimulates mucus production in a neuraminidase-dependent manner. Thus, an increase production of mucus containing secretions appears to be balanced, in vivo, by decreased mucus binding. We postulate that through the combined activity of its neuraminidases, Spn evades mucus binding and mucociliary clearance, which is needed to counter neuraminidase-mediated stimulation of mucus secretions.

Protection of human upper respiratory tract cell lines against sulphur mustard toxicity by hexamethylenetetramine (HMT)

1998 ◽  
Vol 17 (7) ◽  
pp. 373-379 ◽  
Author(s):  
D J Andrew ◽  
C D Lindsay
Keyword(s):  
Respiratory Tract ◽  
Cell Lines ◽  
Chemical Warfare Agent ◽  
Chemical Warfare ◽  
Upper Respiratory Tract ◽  
Sulphur Mustard ◽  
Human Lung Cells ◽  
Effective Prophylaxis ◽  
Upper Respiratory

1. Sulphur mustard (`mustard gas', HD) is a highly toxic chemical warfare agent which affects the skin and respiratory tract. The primary targets of inhaled HD are the epithelia of the upper respiratory tract. Hexamethylenetetramine (HMT) has been shown to protect human lung cells against HD toxicity and has also been shown to be effective in vivo against the chemical warfare agent phosgene. The ability of HMT to protect against the toxicity of HD was investigated in the human upper respiratory tract cell lines BEAS-2B and RPMI 2650. 2. HD was highly toxic to both cell lines, with LC50 values of 15 - 30 mM. HMT, at a concentration of 10 mM, was shown to protect the cell lines against the toxic effects of 20 mM and 40 mM HD. Results demonstrated that it was necessary for HMT to be in situ at the time of exposure to HD for effective cytoprotection. No protection was seen when cells were treated with HMT following exposure to HD, or where HMT was removed prior to HD exposure. 3. Results suggest that HMT may be effective prophylaxis for exposure to HD by inhalation.

scholarly journals Infectious Laryngotracheitis Virus Viral Chemokine-Binding Protein Glycoprotein G Alters Transcription of Key Inflammatory Mediators In Vitro and In Vivo

2017 ◽  
Vol 92 (1) ◽  
Author(s):  
Mauricio J. C. Coppo ◽  
Joanne M. Devlin ◽  
Alistair R. Legione ◽  
Paola K. Vaz ◽  
Sang-Won Lee ◽  
...  
Keyword(s):  
Immune Responses ◽  
Binding Protein ◽  
Upper Respiratory Tract ◽  
Infectious Laryngotracheitis Virus ◽  
Glycoprotein G ◽  
Infectious Laryngotracheitis ◽  
Upper Respiratory ◽  
Laryngotracheitis Virus

ABSTRACTInfectious laryngotracheitis virus (ILTV) is an alphaherpesvirus that infects chickens, causing upper respiratory tract disease and significant losses to poultry industries worldwide. Glycoprotein G (gG) is a broad-range viral chemokine-binding protein conserved among most alphaherpesviruses, including ILTV. A number of studies comparing the immunological parameters between infection with gG-expressing and gG-deficient ILTV strains have demonstrated that expression of gG is associated with increased virulence, modification of the amount and the composition of the inflammatory response, and modulation of the immune responses toward antibody production and away from cell-mediated immune responses. The aims of the current study were to examine the establishment of infection and inflammation by ILTV and determine how gG influences that response to infection.In vitroinfection studies using tracheal organ tissue specimen cultures and blood-derived monocytes andin vivoinfection studies in specific-pathogen-free chickens showed that leukocyte recruitment to the site of infection is an important component of the induced pathology and that this is influenced by the expression of ILTV gG and changes in the transcription of the chicken orthologues of mammalian CXC chemokine ligand 8 (CXCL8), chicken CXCLi1 and chicken CXCLi2, among other cytokines and chemokines. The results from this study demonstrate that ILTV gG interferes with chemokine and cytokine transcription at different steps of the inflammatory cascade, thus altering inflammation, virulence, and the balance of the immune response to infection.IMPORTANCEInfectious laryngotracheitis virus is an alphaherpesvirus that expresses gG, a conserved broad-range viral chemokine-binding protein known to interfere with host immune responses. However, little is known about how gG modifies virulence and influences the inflammatory signaling cascade associated with infection. Here, data fromin vitroandin vivoinfection studies are presented. These data show that gG has a direct impact on the transcription of cytokines and chemokine ligandsin vitro(such as chicken CXCL8 orthologues, among others), which explains the altered balance of the inflammatory response that is associated with gG during ILTV infection of the upper respiratory tract of chickens. This is the first report to associate gG with the dysregulation of cytokine transcription at different stages of the inflammatory cascade triggered by ILTV infection of the natural host.

Functional characterization of VC1929 of Vibrio cholerae El Tor: role in mannose-sensitive haemagglutination, virulence and utilization of sialic acid

Microbiology ◽  
2011 ◽  
Vol 157 (11) ◽  
pp. 3180-3186 ◽  
Author(s):  
Sandeep K. Sharma ◽  
The Su Moe ◽  
Ranjana Srivastava ◽  
Deepak Chandra ◽  
Brahm S. Srivastava
Keyword(s):  
Sialic Acid ◽  
Carbon Source ◽  
Vibrio Cholerae ◽  
Sole Carbon Source ◽  
Minimal Medium ◽  
Adenine Nucleotide ◽  
Functional Characterization ◽  
Acetylneuraminic Acid ◽  
Human Red Blood Cells ◽  
El Tor

The nonadhesive mutant CD11 of Vibrio cholerae El Tor, defective in expression of mannose-sensitive haemagglutinin, lacks a protein when compared with its parent strain. Determination of the amino acid sequence revealed the identity of the protein as the product of VC1929, which is annotated to encode a protein, DctP, involved in the transport of C4-dicarboxylates. We cloned the dctP gene in pUC19 vector and expressed it in mutant CD11. Expression of DctP in the resulting complemented strain restored virulence, adhesive and colonizing capabilities, mannose-sensitive haemagglutination (MSHA) and ability to grow in medium containing sialic acid as a sole carbon source. The mutation in CD11 was caused by insertion of an adenine nucleotide in the reading frame of dctP. Recombinant purified DctP protein showed MSHA of human red blood cells, and protected rabbits against infection by V. cholerae. The protein was localized in membrane and cell wall fractions. The mutant, recombinant CD11 expressing DctP and parent strains were grown in M9 minimal medium in the presence of various carbohydrates (glucose, malate, fumarate, succinate or N-acetylneuraminic acid). The mutant was unable to grow in minimal medium containing N-acetylneuraminic acid (sialic acid) as the sole carbon source whereas the recombinant and parent strains utilized all the sugars tested. It is concluded that DctP is a mannose-sensitive haemagglutinin and a virulence factor and is involved in the utilization of sialic acid.

scholarly journals Identification of an ATPase, MsmK, Which Energizes Multiple Carbohydrate ABC Transporters in Streptococcus pneumoniae

2011 ◽  
Vol 79 (10) ◽  
pp. 4193-4200 ◽  
Author(s):  
Carolyn Marion ◽  
Andrew E. Aten ◽  
Shireen A. Woodiga ◽  
Samantha J. King
Keyword(s):  
Streptococcus Pneumoniae ◽  
Sialic Acid ◽  
Abc Transporter ◽  
Abc Transporters ◽  
Community Acquired Pneumonia ◽  
Bacterial Survival ◽  
Carbohydrate Source ◽  
Content Type ◽  
Airway Colonization

ABSTRACTStreptococcus pneumoniaeis the leading cause of community-acquired pneumonia and results in over 1 million deaths each year worldwide. Asymptomatic colonization of the airway precedes disease, and acquisition of carbohydrates from the host environment is necessary for bacterial survival. We previously demonstrated thatS. pneumoniaecleaves sialic acid from human glycoconjugates to be used as a carbohydrate source. ThesatABCgenes are required for growth and import of sialic acid. ThesatABCgenes are predicted to encode components of an ABC transporter but not the ATPases essential to energize transport. As this subunit is essential, an ATPase must be encoded elsewhere in the genome. We identifiedmsmKas a candidate based on similarity to other known carbohydrate ATPases. Recombinant MsmK hydrolyzed ATP, revealing that MsmK is an ATPase. AnmsmKmutant was reduced in growth on and transport of sialic acid, demonstrating that MsmK is the ATPase energizing the sialic acid transporter. In addition to satABC,S. pneumoniaecontains five other loci that are predicted to encode CUT1 family carbohydrate ABC transporter components; each of these lacks a predicted ATPase. Data indicate thatmsmKis also required for growth on raffinose and maltotetraose, which are the substrates of two other characterized carbohydrate ABC transporters. Furthermore, anmsmKmutant was reduced in airway colonization. Together, these data imply thatin vivo, MsmK energizes multiple carbohydrate transporters inS. pneumoniae. This is the first demonstration of a shared ATPase in a pathogenic bacterium.

Antiviral Properties of Food Plants Could Help to Reduce Contagion and Severity in SARS-CoV-2 Infections

2021 ◽  
Vol 07 ◽  
Author(s):  
Betina Cardoso
Keyword(s):  
Respiratory Tract ◽  
Literature Search ◽  
Food Plants ◽  
Upper Respiratory Tract ◽  
Site Specific ◽  
In Vivo Experiments ◽  
Upper Respiratory ◽  
Novel Coronavirus

Introduction: The importance of an immediate tool to help patients and prevent viral diffusion of new pneumonia caused by 2019 novel coronavirus (2019-nCoV or SARS-CoV-2) that causes the disease COVID-19 becomes evident. Recent articles have reported on body site-specific SARS-CoV-2 infection, showing very active replication in the throat and upper respiratory tract when symptoms were still mild, and thus being efficient in viral transmission in sputum. Material and Methods: An alternative that may be feasible is to resort to scientific studies that demonstrate the antiviral potential of medicinal plants species through in-vitro and in-vivo experiments to alleviate symptoms and prevent the spread of contagion. A literature search in Scopus and PubMed on herbs and foods with antiviral properties was performed. Results: Herbs and foods with demonstrated antiviral potential have been identified, which could limit SARS-CoV-2 spreading by interfering on ACE2 protein on infection sites. The analysis of transdisciplinary knowledge allows us to connect previous research on the action of common plants and foods on viruses to limit the replication of SARS-CoV-2 in the throat and upper respiratory tract. Conclusions: Herbs and foods with demonstrated antiviral potential have been identified, which could limit SARS-CoV-2 spreading by interfering on ACE2 protein on infection sites. The analysis of transdisciplinary knowledge allows us to connect previous research on the action of common plants and foods on viruses to limit the replication of SARS-CoV-2 in the throat and upper respiratory tract.

A Review of Topical Povidone-iodine to Decrease Viral Load of COViD-19

2021 ◽  
Vol 36 (5) ◽  
pp. 238-241
Author(s):  
Katherine M. Benson ◽  
Amalia A. Mancini ◽  
Michael R. Brodeur
Keyword(s):  
Viral Load ◽  
Respiratory Tract Infections ◽  
Povidone Iodine ◽  
Preventive Measure ◽  
Upper Respiratory Tract ◽  
Upper Respiratory ◽  
Clinical Trial Results ◽  
Tract Infections

Topical povidone-iodine (PVP-I) is currently being considered as a potential preventive measure against the spread of COVID-19. Diluted PVP-I solutions have been historically used in Asia to treat upper respiratory tract infections (URTIs) by decreasing the bacterial and viral load on oropharyngeal mucosa to decrease the transmission of diseases. Efficacy of gargling 0.23% PVP-I mouthwash in Japan demonstrated to be efficacious in lowering the prevalence of URTIs when compared with placebo. The 0.23% concentration was used in vitro on severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome coronavirus, which produced undetectable results after 30 seconds of exposure. Additionally, a recent study in 2020 proved the efficacy of PVP-I 0.45%-10% in reducing COVID-19 (SARS-CoV 2) viral load in vitro. Numerous clinical trials are being conducted to determine if there is a decrease in viral load, and thus transmission, when using oral or nasal topical PVP-I in COVID-19 patients. Because of the current lack of evidence for the use of PVP-I in vivo with COVID-19, it is recommended to await the clinical trial results before initiating this practice.

scholarly journals Recombinant Respiratory Syncytial Virus That Does Not Express the NS1 or M2-2 Protein Is Highly Attenuated and Immunogenic in Chimpanzees

2000 ◽  
Vol 74 (19) ◽  
pp. 9317-9321 ◽  
Author(s):  
Michael N. Teng ◽  
Stephen S. Whitehead ◽  
Alison Bermingham ◽  
Marisa St. Claire ◽  
William R. Elkins ◽  
...  
Keyword(s):  
Protective Efficacy ◽  
Neutralizing Antibody ◽  
Target Population ◽  
Large Deletion ◽  
Upper Respiratory Tract ◽  
Wild Type ◽  
Upper Respiratory ◽  
Syncytial Virus

ABSTRACT Mutant recombinant respiratory syncytial viruses (RSV) which cannot express the NS1 and M2-2 proteins, designated rA2ΔNS1 and rA2ΔM2-2, respectively, were evaluated as live-attenuated RSV vaccines. The rA2ΔNS1 virus contains a large deletion that should have the advantageous property of genetic stability during replication in vitro and in vivo. In vitro, rA2ΔNS1 replicated approximately 10-fold less well than wild-type recombinant RSV (rA2), while rA2ΔM2-2 had delayed growth kinetics but reached a final titer similar to that of rA2. Each virus was administered to the respiratory tracts of RSV-seronegative chimpanzees to assess replication, immunogenicity, and protective efficacy. The rA2ΔNS1 and rA2ΔM2-2 viruses were 2,200- to 55,000-fold restricted in replication in the upper and lower respiratory tracts but induced a level of RSV-neutralizing antibody in serum that was only slightly reduced compared to the level induced by wild-type RSV. The replication of wild-type RSV in immunized chimpanzees after challenge was reduced more than 10,000-fold at each site. Importantly, rA2ΔNS1 and rA2ΔM2-2 were 10-fold more restricted in replication in the upper respiratory tract than was thecpts248/404 virus, a vaccine candidate that retained mild reactogenicity in the upper respiratory tracts of 1-month-old infants. Thus, either rA2ΔNS1 or rA2ΔM2-2 might be appropriately attenuated for this age group, which is the major target population for an RSV vaccine. In addition, these results show that neither NS1 nor M2-2 is essential for RSV replication in vivo, although each is important for efficient replication.

A rat nasal epithelial model for predicting upper respiratory tract toxicity: in vivo–in vitro correlations

Toxicology ◽  
2000 ◽  
Vol 145 (1) ◽  
pp. 39-49 ◽  
Author(s):  
J.D Kilgour ◽  
S.A Simpson ◽  
D.J Alexander ◽  
C.J Reed
Keyword(s):  
Respiratory Tract ◽  
Upper Respiratory Tract ◽  
Upper Respiratory
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